This RO1 application seeks five years of support to conduct a molecular genetics study of an existing community-based sample of over 2,400 participants including 500 cohort members (G2 targets), their close- aged siblings, their parents (G1), their romantic partners, and their oldest biological child (G3). The broad objective of this proposal is to evaluate genetic (G), environmental (E), and gene x environment interaction (GxE) effects on a set of core personality attributes that are linked to a host of important developmental outcomes using a weighted, family-based genome-wide association study (GWAS). Specifically, we propose to examine genetic and environmental contributions to the latent traits of Behavioral Disinhibition (BD) and Dispositional Resilience (DR). BD reflects excessive pursuit of exciting appetitive stimuli, disregard for the aversive consequences of risky behaviors, and a tendency to engage in aggressive acts that demonstrate a lack of concern for others. Conversely, DR reflects emotional stability, interpersonal sensitivity, and a self-confident and self-directed orientation to meeting achievement-related challenges. These attributes are present as early as toddlerhood and continue to have important developmental consequences across the life course. In particular these attributes influence whether individuals develop specific competencies and strong interpersonal relationships or whether individuals develop problems that can significantly impair their health and well-being such as involvement with substances, crime, and engaging in risky behaviors. To address these important questions, we will use both existing data from the Family Transitions Project (FTP) as well as genetic information to be collected as part of the proposed study. The FTP was initiated in 1989 when the G2 targets were early adolescents and has continued with annual assessments since that time. The G2 cohort members now average 33 years of age. Each generation in the study has been assessed over a several year period of time using a measurement strategy that is both extensive (i.e., covers multiple domains of personal and social characteristics) and intensive (i.e., employs a multi- informant approach that includes self-reports, other family member reports, teacher reports, ratings by trained observers, school records and public records). Requested funds will be used to collect DNA and genotype the FTP participants. Genotypic information will be combined with the existing archive of contextual and phenotypic data to evaluate genetic and environmental influences on BD and DR. In particular, the unique family structures in this sample include genetically-informative parent-offspring (both G1-G2 and G2-G3) and sibling relationships (G2) which will be ideal for Family-Based Association Test (FBAT) methods. PUBLIC HEALTH RELEVANCE: The goal of the current study is to increase understanding of genetic and environmental factors that shape specific personal attributes that are linked with both maladaptive and adaptive developmental outcomes across the life span. Attributes such as achievement motivation, interpersonal sensitivity, and a positive identity tend to promote successful adaptation, whereas attributes linked with behavioral disinhibition are associated with substance use, crime, health risks, and interpersonal difficulties. The clarification of the genetic and environmental underpinnings of these traits has the potential for enormous public health benefits. Indeed, results from the proposed study should provide specific insights that can inform prevention and treatment efforts designed to promote healthy human development and to reduce psychopathology and problem behaviors.